关键词： ACE2, angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 AD, Alzheimer's disease ADP, adenosine diphosphate ADRD, AD-related dementias Aβ, amyloid β CSF, cerebrospinal fluid Circadian regulation DAMPs DAMPs, damage-associated molecular patterns Diabetes ER, estrogen receptor ETC, electron transport chain FCCP, trifluoromethoxy carbonylcyanide phenylhydrazone FPR-1, formyl peptide receptor 1 GIP, glucose-dependent insulinotropic polypeptide GLP-1, glucagon-like peptide-1 HBP, hexoamine biosynthesis pathway HTRA, high temperature requirement A Hexokinase biosynthesis pathway I3A, indole-3-carboxaldehyde IRF-3, interferon regulatory factor 3 LC3, microtubule associated protein light chain 3 LPS, lipopolysaccharide LRR, leucine-rich repeat MAVS, mitochondrial anti-viral signaling MCI, mild cognitive impairment MRI, magnetic resonance imaging MRS, magnetic resonance spectroscopy Mdivi-1, mitochondrial division inhibitor 1 Microbiome Mitochondrial DNA Mitochondrial electron transport chain Mitochondrial quality control NLRP3, leucine-rich repeat (LRR)-containing protein (NLR)-like receptor family pyrin domain containing 3 NOD, nucleotide-binding oligomerization domain NeuN, neuronal nuclear protein PET, fluorodeoxyglucose (FDG)-positron emission tomography PKA, protein kinase A POLβ, the base-excision repair enzyme DNA polymerase β ROS, reactive oxygen species Reactive species SAMP8, senescence-accelerated mice SCFAs, short-chain fatty acids SIRT3, NAD-dependent deacetylase sirtuin-3 STING, stimulator of interferon genes STZ, streptozotocin SkQ1, plastoquinonyldecyltriphenylphosphonium T2D, type 2 diabetes TCA, Tricarboxylic acid TLR9, toll-like receptor 9 TMAO, trimethylamine N-oxide TP, tricyclic pyrone TRF, time-restricted feeding cAMP, cyclic adenosine monophosphate cGAS, cyclic GMP/AMP synthase hAPP, human amyloid precursor protein hPREP, human presequence protease i.p., intraperitoneal mTOR, mechanistic target of rapamycin mtDNA, mitochondrial DNA αkG, alpha-ketoglutarate

来  源：   DOI：10.1016/j.apsb.2021.06.014   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
Aging is by far the most prominent risk factor for Alzheimer\'s disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.
摘要：
到目前为止，衰老是阿尔茨海默病（AD）最突出的危险因素，衰老和AD都与明显的代谢改变有关。由于开发有效的治疗干预措施来治疗AD显然是迫切需要的，在临床前模型和人类患者中调节全身和细胞内代谢的影响，关于疾病的发病机理，已经被探索过了。人们对与生物性别有关的不同风险和潜在目标策略的认识也越来越高，微生物组,和昼夜节律调节。作为细胞内代谢的重要组成部分，线粒体生物能学，线粒体质量控制机制，和线粒体相关的炎症反应已被考虑用于AD治疗干预。这篇综述总结并强调了这些努力。
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